Relationship between plasma exosomal miR-346 and treatment outcomes in patients with multidrug resistant pulmonary tuberculosis / 中国热带医学

ABSTRACT

@#Abstract： Objective　To investigate the relationship between plasma exosomal microRNA (miRNA)-346 and treatment outcomes in patients with multidrug-resistant tuberculosis (MDR-TB), to provide more reference basis for the treatment of MDR-TB patients. Methods　A total of 406 patients with MDR-TB admitted to Tuberculosis Control and Prevention Institute of Shaanxi Provincial between January 2018 and May 2021 were selected as the study subjects. General clinical data of the patients were collected and analyzed. The expression level of plasma exosomal miR-346 was detected by real-time fluorescence quantitative polymerase chain reaction. The predictive value of plasma exosomal miR-346 for treatment outcome was analyzed using receiver operating characteristic (ROC) curve analysis. Furthermore, the relationship between the expression of plasma exosomal miR-346 and treatment outcome was analyzed using a multivariable logistic regression model. After standard treatment, patients were divided into good treatment outcome group (n=226) and poor treatment outcome group (n=180) according to the treatment outcome. Results　Typical exosomes were identified by transmission electron microscopy, particle size analysis and Western blot, that is, plasma exosomes were successfully extracted. In the poor treatment outcome group, more patients were complicated with diabetes or HIV infection, and the proportion of patients with pulmonary cavity, acid-fast bacilli smear positive rate >1+, previous treatment history and fluoroquinolone resistance was also significantly increased, and the levels of white blood cells, neutrophils, and monocytes were significantly increased, while the level of albumin was significantly decreased, with statistical significance (P>0.05). Compared with the good treatment outcome group [0.61 (0.46, 0.74)], the expression level of plasma exosomal miR-346 in the poor treatment outcome group [1.23 (0.60, 2.02)] was significantly higher (Z=-13.185, P<0.001). ROC curve analysis showed that the area under the curve of plasma exosomal miR-346 to predict adverse outcomes of MDR-TB treatment was 0.881 (95%CI 0.846-0.915), with a sensitivity of 78.3% and specificity of 86.7%. The corresponding cut-off value was 0.81. Multivariate logistic regression analysis showed that diabetes, AIDS virus infection, pulmonary cavity, AFB smear positive degree>1+, previous treatment history, fluoroquinolones resistance and high expression of plasma exosomal miR-346 were independent influencing factors for poor treatment results of MDR-TB (P<0.05). Conclusions　High expression of plasma exosomal miR-346 is associated with the high risk of adverse outcome of MDR-TB treatment, and it is promising to be a useful marker for predicting the outcome of MDR-TB treatment.